Patient Safety Tip of the Week

January 27, 2015

The Golden Hour for Stroke Thrombolysis


Patients with acute ischemic stroke who are candidates for intravenous thrombolytic therapy benefit most when thrombolytic therapy can be accomplished in a more timely fashion. Though the “window” for thrombolytic therapy may be as long as 4.5 hours, those that do best are those who receive thrombolytic therapy within the first 60 minutes from onset of symptoms, termed the “golden hour”. A recent meta-analysis by the Stroke Thrombolysis Trialists' Collaboration showed that the likelihood ratio of a good stroke outcome (modified Rankin score of 0 or 1) was 1.85 when tPA was given within the first hour and decreased to 1.2 when given at 5 hours (Sandercock 2014). Unfortunately, very few patients are actually treated within the golden hour.


Exciting results of an ad hoc subgroup analysis were recently published (Ebinger 2015). The PHANTOM-S study (Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke study) was a prospective controlled study conducted in Berlin, Germany, within an established infrastructure for stroke care. A unique aspect of the study was deployment of a specialized ambulance (the stroke emergency mobile unit or STEMO). This was an ambulance fitted with a mobile CT scanner and point-of-care lab testing and manned by a neurologist, paramedic, and radiology technician. The study was randomized not at the patient level but rather by the weeks according to the availability of the STEMO.


The substudy analyzed thrombolytic therapy rates and found use of STEMO increased the percentage of patients receiving thrombolysis within the golden hour, did not increase the risk to the patients’ safety, and was associated with better short-term outcomes. Thrombolysis rates in ischemic stroke were 32.6% when STEMO was deployed compared to 22.0% when conventional care was administered. Among all patients who received thrombolysis, the proportion of golden hour thrombolysis was 6-fold higher after STEMO deployment (31.0% vs. 4.9%). They were also more likely to be discharged home and had lower 7-day and 90-day mortality rates, though the mortality rate differences did not reach statistical significance. Though the study does not yet have long term outcomes, it is very likely that those will also be better in the group receiving STEMO care and “golden hour” thrombolysis.


This is really exciting work but it will likely be several years before emergency systems and hospitals in the US might be prepared to institute STEMO’s and associated equipment, staffing and protocols.


There is one group of patients who theoretically should be ideal for thrombolytic therapy within the golden hour: those patients having a stroke while already an inpatient in the hospital.


But in our March 18, 2014 Patient Safety Tip of the Week “Systems Approach Improving Stroke Care” we noted a study that mentioned times to treatment are often paradoxically increased in patients having in-hospital strokes (Meretoja 2012). And in our September 23, 2014 Patient Safety Tip of the Week “Stroke Thrombolysis: Need to Focus on Imaging-to-Needle Time” we noted a study (Sauser 2014) that had the interesting observation that decisions take longer when the physician has more time available. Those authors also noted prior studies have demonstrated patients with shorter onset-to-arrival (OTA) times often have longer door-to-needle (DTN) times.


A very telling study was recently presented as an abstract at the Canadian Stroke Congress 2014 (Saltman 2014). Researchers assessed data from 11 regional stroke centers in Ontario, Canada and compared 1048 patients who had strokes while already an inpatient to 32,227 patients who had a stroke elsewhere and were brought to the hospital. Time from symptom recognition to CT scan was 4.5 hours on average for those with in-hospital strokes compared to 1.3 hours for patients brought to the emergency department with a stroke. Only 12% of eligible patient with in-hospital strokes received thrombolytic therapy compared to 19% of those from the community. Moreover, of those receiving thrombolytic therapy only 29% of those with in-hospital stroke received thrombolytic therapy within 90 minutes compared to 72% for those admitted from the community. The in-hospital stroke patients had longer lengths of stay, were less likely to be discharged home, and more likely to be discharged to a rehabilitation facility. These held up even after adjustment for variables such as age, sex, vascular comorbidities, stroke severity and type of stroke.


The authors note that in some cases the symptoms and signs of stroke might be masked in patients already admitted (eg. they might be on a ventilator, be sedated, etc.). But they note that, in general, physicians and staff caring for inpatients are less likely than those in the emergency department or prehospital community to be aware of the protocols for urgent care of stroke patients.


The December 2014 AHRQ Web M&M also had a case study of a patient who suffered a stroke 2 days into a hospital admission (Barrett 2014). It has a good discussion on the protocols we use for managing acute ischemic stroke patients. It mentions several of the barriers to timely assessment and management that we’ve previously discussed in our Patient Safety Tips of the Week for November 6, 2012 “Using LEAN to Improve Stroke Care” and March 18, 2014 “Systems Approach Improving Stroke Care” and September 23, 2014 “Stroke Thrombolysis: Need to Focus on Imaging-to-Needle Time”. These include getting timely imaging studies, drawing and getting lab results in an expedited manner, image interpretation, decision making, ordering and preparing tPA, discussion and informed consent with the patient and family, and administering the tPA. In addition, personnel on inpatient services may be more likely to require neurological consultation than emergency physicians well-trained to handle acute strokes. Or the stroke neurologist on-call may be immediately notified by a stroke alert when a patient is coming to the ED but inpatient staff may not know how to trigger that stroke alert.


In an article about integrating quality improvement into CME activities, Eiser and colleagues noted how discussion at an M&M rounds about a stroke occurring in an inpatient led to recognition that not all clinicians were as familiar with the “stroke alert” process as were emergency physicians (Eiser 2013). This led to dissemination of information about the concept of stroke alert and the protocol procedure to all medical staff, with additional communications to resident physicians via residency program directors.


So few eligible patients are in a position to receive thrombolytic therapy for their acute ischemic stroke within the “golden hour”. It is a shame that those who could most likely be managed in that therapeutic time window are slipping through the cracks in our complex medical system. Does your organization have protocols in place to alert the appropriate stroke team and manage patients expediently when they have a stroke while in the hospital? And are your staff (medical, nursing, residents, etc.) aware of those protocols and the need to intervene immediately?



Some of our previous columns on improving stroke care:

 November 6, 2012     Using LEAN to Improve Stroke Care

 March 18, 2014          Systems Approach Improving Stroke Care

 Septembrer 23, 2014 “Stroke Thrombolysis: Need to Focus on Imaging-to-Needle Time







Sandercock P, on behalf of the Stroke Thrombolysis Trialists' Collaboration. 9th World Stroke Congress (WSC). Session FC01 (no abstract number). Presented October 23, 2014

As reported in Medscape. Keller DM. Early Thrombolysis Reduces Post-stroke Disability. Medscape November 11, 2014



Ebinger M, Kunz A, Wendt M, et al. Effects of Golden Hour Thrombolysis. A Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) Substudy. JAMA Neurol 2015; 72(1): 25-30



Sauser K, Levine DA, Nickles AV, Reeve MJ. Hospital Variation in Thrombolysis Times Among Patients With Acute Ischemic StrokeThe Contributions of Door-to-Imaging Time and Imaging-to-Needle Time. JAMA Neurol. 2014; 71(9): 1155-1161



Meretoja A, Strbian D, Mustanoja S, et al. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 2012; 79: 306–313



Saltman A, et al. Canadian Stroke Congress. Presented October 6, 2014. Abstract 8094

In-Hospital Stroke Patients Wait Longer for Care. as reported in Medscape Oct 09, 2014.

Also reported in Canadian Stroke Congress. Code Stroke on the Ward. Press Release October 6, 2014



Barrett KM. A Stroke of Error. AHRQ Web M&M. December 2014



Eiser AR, McNamee WB, Miller JY. Integrating Quality Improvement Into Continuing Medical Education Activities Within a Community Hospital System. American Journal of Medical Quality 2013; 28(3): 238-242, first published on September 13, 2012





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